Synthesis 2025; 57(15): 2278-2288
DOI: 10.1055/a-2518-1063
short review

Recent Advances in Single Electron Reduction Induced Ring Opening of N-Acyl Cyclic Amines

Kazuhiro Aida
a   Department of Applied Chemistry, Waseda University, 513 Wasedatsurumakicho, Shinjuku, Tokyo 162-0041, Japan
,
Eisuke Ota
b   Waseda Institute for Advanced Study, Waseda University, 513 Wasedatsurumakicho, Shinjuku, Tokyo 162-0041, Japan
,
a   Department of Applied Chemistry, Waseda University, 513 Wasedatsurumakicho, Shinjuku, Tokyo 162-0041, Japan
› Institutsangaben

This work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI) Grant Numbers JP21H05213 (Digi-TOS) (to J.Y.), JP23K13752 (to E.O.), The Uehara Memorial Foundation (to E.O.), and Satomi Foundation (to E.O.). This work was partly supported by the Japan Science and Technology Agency (JST ERATO) Grant Number JPMJER1901 (to J.Y.).


Preview

Abstract

Cyclic amines represent ubiquitous structural motifs in organic chemistry, prominently featured in natural products and pharmaceuticals. The development of synthetic methodologies targeting cyclic amines has attracted considerable interest, given their significance in medicinal chemistry. These transformations can be broadly categorized into two main types: (1) peripheral modification and (2) skeletal remodeling. Recent advancements in late-stage C–H functionalization have showcased the synthetic potential of peripheral modification strategies. Conversely, skeletal remodeling, particularly through the ring opening of cyclic amines, has emerged as a powerful approach to access structurally diverse amines. Ring opening of cyclic amines, initiated by C–N bond cleavage, predominantly relies on two-electron mechanisms. Strained cyclic amines readily undergo such transformations, while those with a larger-membered ring, like pyrrolidines, present greater challenges. Oxidative and von Braun-type approaches have facilitated heterolytic C–N bond cleavage, offering broad applicability across various cyclic amines. In contrast, reductive approaches, which enable homolytic C–N bond cleavage, provide unique access to radical-mediated transformations. This short review highlights recent progress in single electron reduction induced ring-opening methodologies, focusing on α-aminoketyl radical generation for selective amide C–N bond cleavage. Advances in the ring opening of aziridines, azetidines, pyrrolidines, and other cyclic amines are discussed, along with their synthetic implications and future prospects.

1 Introduction

2 Ring Opening of Aziridines

2.1 Hydrogenation and Alkylation

2.2 Isomerization

2.3 Arylation

3 Ring Opening of Azetidines

4 Ring Opening of Pyrrolidines and Other Cyclic Amines

5 Conclusion and Outlook



Publikationsverlauf

Eingereicht: 24. Dezember 2024

Angenommen nach Revision: 16. Januar 2025

Accepted Manuscript online:
16. Januar 2025

Artikel online veröffentlicht:
05. März 2025

© 2025. Thieme. All rights reserved

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Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 
  • References

  • 1 Campos KR. Chem. Soc. Rev. 2007; 36: 1069
  • 2 Mitchell EA, Peschiulli A, Lefevre N, Meerpoel L, Maes BU. W. Chem. Eur. J. 2012; 18: 10092
  • 3 Cordier CJ, Lundgren RJ, Fu GC. J. Am. Chem. Soc. 2013; 135: 10946
  • 4 He Y, Zheng Z, Yang J, Zhang X, Fan X. Org. Chem. Front. 2021; 8: 4582
  • 5 Chen W, Paul A, Abboud KA, Seidel D. Nat. Chem. 2020; 12: 545
  • 6 Shaw MH, Shurtleff VW, Terrett JA, Cuthbertson JD, MacMillan DW. C. Science 2016; 352: 1304
  • 7 Roque JB, Kuroda Y, Göttemann LT, Sarpong R. Nature 2018; 564: 244
  • 8 Kennedy SH, Dherange BD, Berger KJ, Levin MD. Nature 2021; 593: 223
  • 9 Jurczyk J, Lux MC, Adpressa D, Kim SF, Lam Y.-H, Yeung CS, Sarpong R. Science 2021; 373: 1004
  • 10 Roque JB, Kuroda Y, Göttemann LT, Sarpong R. Science 2018; 361: 171
  • 11 Roque JB, Sarpong R, Musaev DG. J. Am. Chem. Soc. 2021; 143: 3889
  • 12 Kaledin AL, Roque JB, Sarpong R, Musaev DG. Top. Catal. 2022; 65: 418
  • 13 Jurczyk J, Woo J, Kim SF, Dherange BD, Sarpong R, Levin MD. Nat. Synth. 2022; 1: 352
  • 14 Yudin AK. Aziridines and Epoxides in Organic Synthesis . Yudin AK. Wiley-VCH; Weinheim: 2006
  • 15 McCoull W, Davis FA. Synthesis 2000; 1347
  • 16 Hu XE. Tetrahedron 2004; 60: 2701
  • 17 Singh GS, D’hooghe M, De Kimpe N. Chem. Rev. 2007; 107: 2080
  • 18 Huang CY, Doyle AG. Chem. Rev. 2014; 114: 8153
  • 19 Sabir S, Kumar G, Verma VP, Jat JL. ChemistrySelect 2018; 3: 3702
  • 20 Chen J, Zhu G, Wu J. Acta Chim. Sin. 2024; 82: 190
  • 21 Furniel LG, Corrêa AG. ChemPhotoChem 2024; 8: e202400120
  • 22 Han G, McIntosh MC, Weinreb SM. Tetrahedron Lett. 1994; 35: 5813
  • 23 Boto A, Hernández R, Suárez E. J. Org. Chem. 2000; 65: 4930
  • 24 Cocquet G, Ferroud C, Guy A. Tetrahedron 2000; 56: 2975
  • 25 Ito R, Umezawa N, Higuchi T. J. Am. Chem. Soc. 2005; 127: 834
  • 26 Kaname M, Yoshifuji S, Sashida H. Tetrahedron Lett. 2008; 49: 2786
  • 27 Osberger TJ, Rogness DC, Kohrt JT, Stepan AF, White MC. Nature 2016; 537: 214
  • 28 Wang H, Man Y, Wang K, Wan X, Tong L, Li N, Tang B. Chem. Commun. 2018; 54: 10989
  • 29 Liu RH, He YH, Yu W, Zhou B, Han B. Org. Lett. 2019; 21: 4590
  • 30 Wu L, Xia H, Bai J, Xi Y, Wu X, Gao L, Qu J, Chen Y. Nat. Chem. 2024; 16: 1951
  • 31 Elderfield RC, Hageman HA. J. Org. Chem. 1949; 14: 605
  • 32 Elderfield RC, Green M. J. Org. Chem. 1952; 17: 431
  • 33 Yu C, Shoaib MA, Iqbal N, Kim JS, Ha HJ, Cho EJ. J. Org. Chem. 2017; 82: 6615
  • 34 Kim Y, Heo J, Kim D, Chang S, Seo S. Nat. Commun. 2020; 11: 4761
  • 35 Su J, Ma X, Ou Z, Song Q. ACS Cent. Sci. 2020; 6: 1819
  • 36 Seong S, Lim H, Han S. Chem 2019; 5: 353
  • 37 Lim H, Seong S, Kim Y, Seo S, Han S. J. Am. Chem. Soc. 2021; 143: 19966
  • 38 Zhang J, Chang S. J. Am. Chem. Soc. 2020; 142: 12585
  • 39 Peng Y, Oestreich M. Chem. Eur. J. 2023; 29: e202203721
  • 40 Zhang Y.-Q, Vogelsang E, Qu Z.-W, Grimme S, Gansäuer A. Angew. Chem. Int. Ed. 2017; 56: 12654
  • 42 Hao W, Wu X, Sun JZ, Siu JC, MacMillan SN, Lin S. J. Am. Chem. Soc. 2017; 139: 12141
  • 43 Boekell NG, Flowers RA. Chem. Rev. 2022; 122: 13447
  • 44 Wu A, Mayer JM. J. Am. Chem. Soc. 2008; 130: 14745
  • 45 Semproni SP, Milsmann C, Chirik PJ. J. Am. Chem. Soc. 2014; 136: 9211
  • 46 Tarantino KT, Miller DC, Callon TA, Knowles RR. J. Am. Chem. Soc. 2015; 137: 6440
  • 47 Zhang Y, Jakoby V, Stainer K, Schmer A, Klare S, Bauer M, Grimme S, Cuerva JM, Gansäuer A. Angew. Chem. Int. Ed. 2016; 55: 1523
  • 48 Wood DP, Guan W, Lin S. Synthesis 2021; 53: 4213
  • 49 Yao C, Williams AD. N, Gu Y, Norton JR. J. Org. Chem. 2022; 87: 4991
  • 50 Williams WL, Gutiérrez-Valencia NE, Doyle AG. J. Am. Chem. Soc. 2023; 145: 24175
  • 52 Li H, Lai Z, Adijiang A, Zhao H, An J. Molecules 2019; 24: 459
  • 53 Mujika JI, Matxain JM, Eriksson LA, Lopez X. Chem. Eur. J. 2006; 12: 7215
  • 54 Szostak M, Spain M, Procter DJ. Angew. Chem. Int. Ed. 2013; 52: 7237
  • 55 Chen L, Qu Q, Ran CK, Wang W, Zhang W, He Y, Liao LL, Ye JH, Yu DG. Angew. Chem. Int. Ed. 2023; 62: e202217918
  • 56 Aida K, Hirao M, Saitoh T, Yamamoto T, Einaga Y, Ota E, Yamaguchi J. J. Am. Chem. Soc. 2024; 146: 30698
  • 57 Singh A, Teegardin K, Kelly M, Prasad KS, Krishnan S, Weaver JD. J. Organomet. Chem. 2015; 776: 51
  • 58 Strieth-Kalthoff F, James MJ, Teders M, Pitzer L, Glorius F. Chem. Soc. Rev. 2018; 47: 7190
  • 59 Kim SF, Schwarz H, Jurczyk J, Nebgen BR, Hendricks H, Park H, Radosevich A, Zuerch MW, Harper K, Lux MC, Yeung CS, Sarpong R. J. Am. Chem. Soc. 2024; 146: 5580